It is commonly felt that hydrochloric acid has a primary role in ulcerogenesis, yet data directly relating cellular pH to metabolic and pericellular variables has not been published. We are using pH sensitive microelectrodes to measure intracellular pH in canine gastric mucosal cells. Once the normal range for these surface cells has been satisfactorily established, we will define the relationship between intracellular pH and lumenal pH under normal and pathological conditions. Additonally, using pO2 microelectrodes, standard blood flow techniques and appropriate biochemical and histological analyses, we will define the interrelationships between gastric blood flow, epithelial pO2 and pH under a variety of conditions such as ischemia, hemorrhagic shock, and sepsis. Subsequently, the effects of various agents of potential therapeutic value such as prostaglandins, fructose 1,6-diphosphate, naloxone and thromboxane synthetase inhibitors on intracellular pH and other physiological determinants of mucosal integrity will be evaluated. Finally, we will adapt the pO2 and pH techniques to the study of the colonic mucosa. The successful accomplishment of the aims of this proposal will supplement work done in this laboratory toward the understanding of the basic physiology and pathophysiology of the gastric and colonic mucosa.